Abstract
The nonstructural protein 3 (NS3) of hepatitis C virus contains a protease domain at its amino terminus and RNA helicase domain at its carboxyl terminus. To identify optimal NS3 protein for developing screening assays, we expressed full-length NS3 protease/helicase and helicase domains from both HCV type 1a (H77 strain) and 1b (Con1 strain), using either E. coli or baculovirus expression systems. Our studies showed that the full-length NS3 proteins, either with or without the presence of the NS4A domain, from either strains were at least 10-fold more efficient than the corresponding helicase domains in unwinding partial duplex RNA substrates. These findings provide a rationale for the use of full-length NS3 in high throughput screening assays to identify potent small molecule inhibitors of this important target of HCV.
Keywords: hcv, ns, protease domain, helicase domain, coli, baculovirus, unwinding activity
Protein & Peptide Letters
Title: The RNA-Unwinding Activity of Hepatitis C Virus Non-Structural Protein 3 (NS3) Is Positively Modulated by Its Protease Domain
Volume: 12 Issue: 4
Author(s): Baohua Gu, Cynthia M. Pruss, Adam T. Gates and Sanjay S. Khandekar
Affiliation:
Keywords: hcv, ns, protease domain, helicase domain, coli, baculovirus, unwinding activity
Abstract: The nonstructural protein 3 (NS3) of hepatitis C virus contains a protease domain at its amino terminus and RNA helicase domain at its carboxyl terminus. To identify optimal NS3 protein for developing screening assays, we expressed full-length NS3 protease/helicase and helicase domains from both HCV type 1a (H77 strain) and 1b (Con1 strain), using either E. coli or baculovirus expression systems. Our studies showed that the full-length NS3 proteins, either with or without the presence of the NS4A domain, from either strains were at least 10-fold more efficient than the corresponding helicase domains in unwinding partial duplex RNA substrates. These findings provide a rationale for the use of full-length NS3 in high throughput screening assays to identify potent small molecule inhibitors of this important target of HCV.
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Cite this article as:
Gu Baohua, Pruss M. Cynthia, Gates T. Adam and Khandekar S. Sanjay, The RNA-Unwinding Activity of Hepatitis C Virus Non-Structural Protein 3 (NS3) Is Positively Modulated by Its Protease Domain, Protein & Peptide Letters 2005; 12 (4) . https://dx.doi.org/10.2174/0929866053765716
DOI https://dx.doi.org/10.2174/0929866053765716 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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